Unique antibody gene signature in Multiple Sclerosis

Abstract Patients with multiple sclerosis (MS), an inflammatory, demyelinating disease of the Central Nervous System (CNS), derive the most benefit from disease modifying pharmacotherapies the earlier they are treated. Patients who have had a single episode of demyelination are at greater risk to develop clinically definite MS, but are not treated for MS, even though diagnosis of clinically definite MS could be significantly delayed if currently approved treatments are initiated immediately after the first attack. Defining biomarkers that identify patients with one demyelinating event who will convert to MS may provide a tool to allow earlier treatment of this "at risk" patient group. We have discovered a unique pattern of somatic mutations in the antibody genes of B cells isolated from the cerebrospinal fluid of patients with MS that can accurately and independently predict patients that subsequently develop definite MS after a single episode of demyelination. This antibody signature represents the first genetic biomarker candidate for MS outside of the MHC locus. If independently confirmed, our observations will have a major impact as a new diagnostic tool in patients with very early demyelinating disease of the CNS. This work was supported by the National Institutes of Health (NIH) to NLM (RO1 NS 40993) and MKR (RO1 NS 37513, RO1 AI 47133, and K24 NS 44250), the National Multiple Sclerosis Society (NMSS) to NLM (RG3267) and JLB (RG3908), the Yellow Rose Foundation (NLM and MKR), the Wadsworth Foundation (to NLM) and Howson funds (to NLM).